Restriction endonuclease analyses of DNA from one Black G gamma A gamma-HPFH homozygote and four Black and one Indian G gamma A gamma-HPFH heterozygotes have identified three different HPFH types which are the result of large deletions including the delta and beta genes. Two of the types are comparable to those characterized previously, but the third, which is present in the Indian heterozygote, shows a distinct difference in the size of the deletion. The 5' end point of the deletion in this type III G gamma A gamma-HPFH extends 0.5-1.0 kb beyond the 5' end point of one of the Black types of HPFH (type I). Each of the three types is associated with a distinct ratio between the G gamma and the A gamma chains, an observation supported by family data. The highest ratio is found in the heterozygote with the Indian type III G gamma A gamma-HPFH, with 69.3% G gamma chains, while the averages for the other types were 50.7% G gamma (type I) and 32.3% G gamma (type II).

The gamma chain compositions of the fetal hemoglobins of 2453 newborn babies from East Asian countries (1350 babies), from Italy, Yugoslavia, Bulgaria, and Georgia (417 Caucasian babies), and 686 black babies from Georgia were determined by high pressure liquid chromatography. Unusual results for a limited number of babies were confirmed by chemical analyses, and were evaluated further by family studies. Statistical analyses indicated high gene frequencies for the A gamma T chain in Italian (f = 0.237), Yugoslavian and Bulgarian (f = 0.238), and white Georgia babies (f = 0.224), a lower frequency in Japan (f = 0.178), and India (f = 0.173), and particularly in mainland China (f = 0.079). The A gamma T gene frequency in normal (AA) Black babies was 0.102. When a beta S or beta C mutation was also present this frequency was greatly decreased, particularly in babies with the AC condition (f = 0.036). These results suggest the near absence of the A gamma T mutation on the chromosome also carrying the beta C determinant. Most babies had the expected G gamma values which vary between 60 and 80%, but several (mainly black) babies had higher values (between 80 and 90%), while one normal black baby had a G gamma value of (nearly) 100%. This condition may be a form of A gamma +1-thalassemia and has been discussed in detail elsewhere (Blood 58:491-500, 1981). Thirty-five clinically normal (mainly Chinese, Indian, and Japanese) babies had G gamma values of about 40%. Twenty-six babies had A gamma I values of about 60%, while the remaining nine babies had A gamma T and A gamma I chains in a ratio of either 1 to 2 or 1 to 1. Two additional newborns did not produce any G gamma chains, but had only A gamma I chains or A gamma T chains. Family studies failed to indicate a specific hematological abnormality. These unusual ratios between the G gamma and A gamma (either A gamma I or A gamma T) chains have led to speculations regarding possible genetic abnormalities present in these infants.

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Summary. The haemoglobin of a 9‐yr‐old boy from the area of Bombay has only haemoglobin F. The γ‐chains of this haemoglobin F are solely of Gγ type, and the child is considered to be a homozygote for hereditary persistence of foetal haemoglobin of the Gγ type. The same kind of haemoglobin F is also present in a second Indian family and in four American Negro families. One Negro family has an appreciably lower percentage of haemoglobin F in heterozygotes than the other five families. In some of the families certain individuals also have haemoglobin E or haemoglobin S in trans to the other condition and haemoglobin A is absent. Although it has been concluded that the hereditary persistence of foetal haemoglobin is present the condition is not expressed uniformly in all these families. Some of them have certain characteristics of F‐thalassaemia. It is possible that two conditions are, in reality, represented: perhaps some families have the hereditary persistence of foetal haemoglobin and others have F‐thalassaemia.

Two sons of a previously reported Ghanaian homozygote for the hereditary persistence of fetal hemoglobin (HPFH) (Ringelhann et al., 1970) also are HPFH homozygotes. In addition, another unrelated adult Ghanaian homozygote has been detected. All of these Ghanaian homozygotes as well as three American Black HPFH homozygotes have the G gamma A gamma type of HPFH with a G gamma to A gamma ratio of about 3:2, in contrast to an Asiatic Indian homozygote who has the G gamma type. Globin chain synthesis in HPFH homozygotes is unbalanced, with a gamma/alpha ratio of 0.6 or less, whereas it is balanced in heterozygotes according to most reports.

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The fetal hemoblobin (Hb F) of a few hundred nonblack patients with a heterozygosity or homozygosity for 0-thalassemia (0-thal), 60-thalassemia (dp-thal), and some forms of the hereditary persistence of Hb F (HPFH) was isolated by DEAE-cellulose chromatography and further characterized by high-pressure liquid chromatography. Quantitative data for the three types of y chain (A?'. A y l , and "7) were compared with those obtained for the H b F from black patients with similar conditions. The G ? chain levels in nonblack 0-thal heterozygotes varied greatly and did not fall into two distinct groups with high or low levels, a5 has been observed in blacks. The level of the Ayrchain in A y r heterozygotes did not differ significantly when this anomaly was in cis or in trans to the B-thal determinant. Beta-thalassemia homozygotes from Turkey and Yugoslavia, had "y values varying between 40% and BOc'io. Only 13 of 34 patients carried the A y r gene. Nine were A y T heterozygotes with an AyT/total *y level averaging 39% and four were A y T homozygotes.The "y chain levels in nonblack GB-thal heterozygotes varied between 28% and 46%.An additional A y T chain heterozygosity in cis to the 60-thal determinant demonstrated that over 90% of t h e r chains is produced by genes in cis to this anomaly. Analyses of members of two relatively large families with B-thal, dfi-thal, and the A y T chain heterozygosities and homozygosities occurring in different combinations allowed a more or less quantitative evaluation of the production of y-chain genes in cis or in trans to either of the two types of thalassemia determinants. Such calculations were possible both in simple heterozygotes and in persons with the P-d/3-thalassemia condition. Efremov et a1The Indian type of GyAy-HPFH heterozygosity was studied in four individuals of whom two were A y r heterozygotes. This condition differs from the black types in higher levels of G y chain and in a considerable contribution of y-chain genes in trans to the H P F H determinant. The Swiss type of HPFH heterozygosity was studied in 30 subjects belonging to six Yugoslavian families; some were A y r heterozygotes. The level of "y chain averaged over 80% in nine members of one family; the anomaly in this family deserves further study.